University of Brest, Brest, France.
Anticancer Res. 2013 May;33(5):2065-75.
Prostate cancer can usually be treated at a clinically localized stage by radical prostatectomy. Unfortunately, within 10 years following surgery, 30% of patients experience local or distant relapse. Few data exist on the association of markers of angiogenesis and distant relapse after radical prostatectomy. By immunohistochemistry in tissue microarray, we compared the expression pattern of hypoxia inducible factor 1, alpha subunit (HIF1α) and vascular endothelial growth factor (VEGF) and its receptors in 45 patients with distant relapse and 68 patients without relapse after radical prostatectomy. Expressions of HIF1α and VEGF were assessed in prostate tumor cells and those of VEGFR1, VEGFR2 and neuropilin 1 in tumor and endothelial cells. The five molecules studied were expressed by all tumors, with the exception of neuropilin 1 in endothelial cells for one tumor. Strong endothelial expression of VEGFR1 appeared to be an independent predictor of distant relapse. A moderate to strong endothelial expression of neuropilin 1 was in turn an independent predictor of absence of distant relapse. No significant difference was found for HIF1α, VEGF, VEGFR1, VEGFR2 and neuropilin 1 expression in tumor cells, nor for VEGFR2 in endothelial cells, between the two groups. To our knowledge, this is the first study to evaluate the prognostic value of VEGFR1, VEGFR2 and neuropilin 1 in endothelial cells in prostate cancer after radical prostatectomy. The evaluation by immunohistochemistry of endothelial expression of neuropilin 1 and VEGFR1 could be an additional tool in the assessment of tumor aggressiveness of clinically localized prostate cancer to better identify patients at high risk of distant relapse.
前列腺癌通常可以通过根治性前列腺切除术在临床局部阶段进行治疗。不幸的是,在手术后 10 年内,30%的患者出现局部或远处复发。关于根治性前列腺切除术后血管生成标志物与远处复发的相关性,数据很少。通过组织微阵列免疫组织化学,我们比较了 45 例远处复发患者和 68 例根治性前列腺切除术后无复发患者的缺氧诱导因子 1α亚单位(HIF1α)和血管内皮生长因子(VEGF)及其受体的表达模式。在肿瘤细胞中评估了 HIF1α和 VEGF 的表达,在肿瘤细胞和内皮细胞中评估了 VEGFR1、VEGFR2 和神经纤毛蛋白 1 的表达。除了一个肿瘤的内皮细胞中没有神经纤毛蛋白 1 外,研究的五种分子均在所有肿瘤中表达。VEGFR1 的强烈内皮表达似乎是远处复发的独立预测因子。反过来,神经纤毛蛋白 1 的中度至强烈内皮表达是远处无复发的独立预测因子。两组之间肿瘤细胞中 HIF1α、VEGF、VEGFR1、VEGFR2 和神经纤毛蛋白 1 的表达以及内皮细胞中 VEGFR2 的表达均无显著差异。据我们所知,这是第一项评估根治性前列腺切除术后前列腺癌中内皮细胞中 VEGFR1、VEGFR2 和神经纤毛蛋白 1 的预后价值的研究。通过免疫组织化学评估神经纤毛蛋白 1 和 VEGFR1 的内皮表达可能是评估临床局限性前列腺癌侵袭性的附加工具,以更好地识别远处复发风险高的患者。